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U.S. FDA Title 21 CFR Part 11 Regulation

21 CFR Part 11 Electronic Records; Electronic Signatures; Final Rule

FDA regulation "21 CFR Part 11 Electronic Records; Electronic Signatures; Final Rule" (referred to here as Part 11) was the result of a six-year effort by FDA (with input from the industry) to supply all FDA-regulated companies with requirements on how to maintain paperless (that is, electronic) record systems while still complying with good clinical, laboratory, and manufacturing practices, such as:

  • GMP: 21 CFR 110 (food), 210 (drugs in general, also includes GMP for biologics), 211 (finished pharmaceuticals), 820 (medical devices)
  • Good laboratory practice (GLP) 58

  • Good clinical practice (GCP) 50, 54, 56

The regulation also details very specific requirements for electronic and digital signatures, because FDA considers these signatures to be legally binding. Since its publication more than nine years ago, this regulation has been subject to evolving interpretations both by FDA and industry. 

In February 2003 FDA withdrew all Part 11 guidelines and the Compliance Policy Guide. The reasons for the withdrawal are discussed in the FDA document from August 2003, "Guidance for Industry Part 11, Electronic Records; Electronic Signatures - Scope and Application," as follows: ". . . concerns have been raised that some interpretations of the part 11 requirements would (1) unnecessarily restrict the use of electronic technology in a manner that is inconsistent with FDA's stated intent in issuing the rule, (2) significantly increase the costs of compliance to an extent that was not contemplated at the time the rule was drafted, and (3) discourage innovation and technological advances without providing a significant public health benefit. These concerns have been raised particularly in the areas of part 11 requirements for validation, audit trails, record retention, record copying, and legacy systems."

Pharmaceutical cGMPs for the 21st Century: A Risk-Based Approach

In August 2002 FDA announced a significant initiative to enhance the regulation of pharmaceutical manufacturing and product quality by applying a scientific and risk-based approach to product quality regulation incorporating an integrated qualitysystems approach to current good manufacturing practice (cGMP). FDA has been developing a more systematic and rigorous, risk-based approach toward compliance and using good science. A justifiable and documented risk assessment, and one that is defensible, has become a predominant theme within FDA's recent initiatives.

New Part 11 Guidance

As mentioned earlier, in August 2003 FDA published the final guidance titled, "Guidance for Industry Part 11, Electronic Records; Electronic Signatures - Scope and Application." The final guidance delineates how FDA intends to re-examine Part 11 and may propose revisions to that regulation.

The approach outlined in the guidance is based upon the following:

  • FDA intends to narrowly interpret the scope of Part 11 in an effort to clarify fewer records to be considered subject to Part 11
  • FDA intends to exercise enforcement discretion with respect to certain Part 11 requirements for both legacy and current systems
  • Predicate rule requirements for records subject to Part 11 will be enforced
  • Hybrid systems necessary to comply with Part 11 requirements are acceptable

What has not changed? FDA's interpretation of the following requirements has not changed:

  • Controls for closed systems
  • Controls for open systems
  • Electronic signatures

Ultimately, companies must comply with applicable predicate rules. Records that FDA requires be maintained or submitted must remain secure and reliable in accordance with the predicate rules.

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